Obstetrics

SNOWMASS, COLO. – Corticosteroids can be thought of as the 'go-to' drugs for the management of rheumatologic disorders in pregnancy.

“Corticosteroids have been my ace in the hole in treating many patients during pregnancy. They're potent immunosuppressives that can get you out of a lot of trouble. And although they can have side effects, if used judiciously they are a reasonable treatment choice,” Dr. Bonnie L. Bermas stressed at the symposium.

Reassuringly, transplant registries comprising many tens of thousands of organ recipients have shown no increased rate of congenital anomalies with the use of corticosteroids in pregnancy.

However, an influential University of Toronto meta-analysis has concluded that “although prednisone does not represent a major teratogenic risk in humans at therapeutic doses, it does increase by an order of 3.4-fold the risk of oral cleft” (Teratology 2000;62:385-92).

“What this translates to in your practice is, the cleft palate incidence increases from 1 in 1,000 in the general population to about 1 in 300 live births exposed to steroids in utero. That's how I counsel my patients who need to be on corticosteroids in the first trimester,” said Dr. Bermas, clinical director of the lupus center at Brigham and Women's Hospital in Boston.

After 12-14 weeks' gestation, however, the palate is formed. And although steroids are no longer associated with an increased risk for cleft palate after that point in gestation, other risks remain. These include gestational diabetes, gestational hypertension, osteoporosis in the mother, premature rupture of the membranes, and small-for-gestational-age infants.

Prednisone and methylprednisolone—the steroids rheumatologists utilize most often—don't cross the placenta efficiently, and hence are much less likely to cause fetal adverse effects than are dexamethasone or betamethasone.

Steroids that are administered to the mother make their way into breast milk only in low concentrations. If she's on less than 20 mg/day of prednisone, she can breastfeed normally. For women on higher doses, Dr. Bermas advises pumping and discarding the breast milk for the first 4 hours after a dose is taken.

Dr. Bermas emphasized that the key to successful treatment of rheumatologic disorders during pregnancy is a clear-eyed assessment of and accommodation to the patient's tolerance for risk—and the physician's, as well.

“There are some women who do not drink caffeinated beverages or take any medications, not even a Tylenol, and who will eat only organic foods while pregnant. There are others who are willing to tolerate some risk during pregnancy. And as clinicians, we have our own risk tolerances, too. For example, azathioprine is a medication that I feel comfortable using during pregnancy, but I have colleagues who won't because they wouldn't be able to sleep at night,” she explained.

The reason she prescribes azathioprine during pregnancy—despite its category D rating from the Food and Drug Administration, indicating “positive evidence of risk”—is that there's an enormous transplant literature showing no increase in congenital anomalies with in utero exposure to this drug.

Mycophenolate mofetil (CellCept) also has a category D rating. But unlike azathioprine, mycophenolate mofetil has no extensive and reassuring transplant literature. As a result, Dr. Bermas said that she avoids it in pregnancy and nursing.

Other rheumatologic medications to avoid in pregnancy are methotrexate, penicillamine, 6-mercaptopurine, and chlorambucil, she continued.

The use of tumor necrosis factor inhibitors during pregnancy is an extremely challenging question. Although at present the FDA rates them as category B (“no evidence of risk in humans”), that could very well change as a result of a reported association (J. Rheumatol. 2009;36:635-41) with VACTERL anomalies, which include vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities. On the other hand, several editorials and review articles have expressed the view that the risk of VACTERL anomaly after in utero exposure is overstated.

When lupus patients on antimalarials become pregnant, Dr. Bermas said she generally keeps them on the medication. She also allows patients to remain on antimalarials while nursing, which is consistent with the position of the American Academy of Pediatrics.

For mild cases of rheumatologic disease in pregnancy, Dr. Bermas reported that she relies on NSAIDs and/or prednisone at 5-10 mg/day. She halts the NSAID after the second trimester in order to avoid premature closure of a patent ductus arteriosus. For an inflammatory mild arthritis, she considers adding sulfasalazine.

She said she manages moderate disease with higher-dose steroids, azathioprine, or cyclosporine. For severe disease, Dr. Bermas reported that she turns to pulse steroids, azathioprine, cyclosporine, or intravenous immunoglobulin. In life-or-death situations, there are many case reports of cyclophosphamide being used successfully in the third trimester, a time by which most organogenesis is completed.

Dr. Bermas reported having no financial conflicts of interest.

“Corticosteroids have been my ace in the hole in treating many patients … [They] can get you out of a lot of trouble.'

Source DR. BERMAS

SNOWMASS, COLO. – Corticosteroids can be thought of as the 'go-to' drugs for the management of rheumatologic disorders in pregnancy.

“Corticosteroids have been my ace in the hole in treating many patients during pregnancy. They're potent immunosuppressives that can get you out of a lot of trouble. And although they can have side effects, if used judiciously they are a reasonable treatment choice,” Dr. Bonnie L. Bermas stressed at the symposium.

Reassuringly, transplant registries comprising many tens of thousands of organ recipients have shown no increased rate of congenital anomalies with the use of corticosteroids in pregnancy.

However, an influential University of Toronto meta-analysis has concluded that “although prednisone does not represent a major teratogenic risk in humans at therapeutic doses, it does increase by an order of 3.4-fold the risk of oral cleft” (Teratology 2000;62:385-92).

“What this translates to in your practice is, the cleft palate incidence increases from 1 in 1,000 in the general population to about 1 in 300 live births exposed to steroids in utero. That's how I counsel my patients who need to be on corticosteroids in the first trimester,” said Dr. Bermas, clinical director of the lupus center at Brigham and Women's Hospital in Boston.

After 12-14 weeks' gestation, however, the palate is formed. And although steroids are no longer associated with an increased risk for cleft palate after that point in gestation, other risks remain. These include gestational diabetes, gestational hypertension, osteoporosis in the mother, premature rupture of the membranes, and small-for-gestational-age infants.

Prednisone and methylprednisolone—the steroids rheumatologists utilize most often—don't cross the placenta efficiently, and hence are much less likely to cause fetal adverse effects than are dexamethasone or betamethasone.

Steroids that are administered to the mother make their way into breast milk only in low concentrations. If she's on less than 20 mg/day of prednisone, she can breastfeed normally. For women on higher doses, Dr. Bermas advises pumping and discarding the breast milk for the first 4 hours after a dose is taken.

Dr. Bermas emphasized that the key to successful treatment of rheumatologic disorders during pregnancy is a clear-eyed assessment of and accommodation to the patient's tolerance for risk—and the physician's, as well.

“There are some women who do not drink caffeinated beverages or take any medications, not even a Tylenol, and who will eat only organic foods while pregnant. There are others who are willing to tolerate some risk during pregnancy. And as clinicians, we have our own risk tolerances, too. For example, azathioprine is a medication that I feel comfortable using during pregnancy, but I have colleagues who won't because they wouldn't be able to sleep at night,” she explained.

The reason she prescribes azathioprine during pregnancy—despite its category D rating from the Food and Drug Administration, indicating “positive evidence of risk”—is that there's an enormous transplant literature showing no increase in congenital anomalies with in utero exposure to this drug.

Mycophenolate mofetil (CellCept) also has a category D rating. But unlike azathioprine, mycophenolate mofetil has no extensive and reassuring transplant literature. As a result, Dr. Bermas said that she avoids it in pregnancy and nursing.

Other rheumatologic medications to avoid in pregnancy are methotrexate, penicillamine, 6-mercaptopurine, and chlorambucil, she continued.

The use of tumor necrosis factor inhibitors during pregnancy is an extremely challenging question. Although at present the FDA rates them as category B (“no evidence of risk in humans”), that could very well change as a result of a reported association (J. Rheumatol. 2009;36:635-41) with VACTERL anomalies, which include vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities. On the other hand, several editorials and review articles have expressed the view that the risk of VACTERL anomaly after in utero exposure is overstated.

When lupus patients on antimalarials become pregnant, Dr. Bermas said she generally keeps them on the medication. She also allows patients to remain on antimalarials while nursing, which is consistent with the position of the American Academy of Pediatrics.

For mild cases of rheumatologic disease in pregnancy, Dr. Bermas reported that she relies on NSAIDs and/or prednisone at 5-10 mg/day. She halts the NSAID after the second trimester in order to avoid premature closure of a patent ductus arteriosus. For an inflammatory mild arthritis, she considers adding sulfasalazine.

She said she manages moderate disease with higher-dose steroids, azathioprine, or cyclosporine. For severe disease, Dr. Bermas reported that she turns to pulse steroids, azathioprine, cyclosporine, or intravenous immunoglobulin. In life-or-death situations, there are many case reports of cyclophosphamide being used successfully in the third trimester, a time by which most organogenesis is completed.

Dr. Bermas reported having no financial conflicts of interest.

“Corticosteroids have been my ace in the hole in treating many patients … [They] can get you out of a lot of trouble.'

Source DR. BERMAS

SNOWMASS, COLO. – Corticosteroids can be thought of as the 'go-to' drugs for the management of rheumatologic disorders in pregnancy.

“Corticosteroids have been my ace in the hole in treating many patients during pregnancy. They're potent immunosuppressives that can get you out of a lot of trouble. And although they can have side effects, if used judiciously they are a reasonable treatment choice,” Dr. Bonnie L. Bermas stressed at the symposium.

Reassuringly, transplant registries comprising many tens of thousands of organ recipients have shown no increased rate of congenital anomalies with the use of corticosteroids in pregnancy.

However, an influential University of Toronto meta-analysis has concluded that “although prednisone does not represent a major teratogenic risk in humans at therapeutic doses, it does increase by an order of 3.4-fold the risk of oral cleft” (Teratology 2000;62:385-92).

“What this translates to in your practice is, the cleft palate incidence increases from 1 in 1,000 in the general population to about 1 in 300 live births exposed to steroids in utero. That's how I counsel my patients who need to be on corticosteroids in the first trimester,” said Dr. Bermas, clinical director of the lupus center at Brigham and Women's Hospital in Boston.

After 12-14 weeks' gestation, however, the palate is formed. And although steroids are no longer associated with an increased risk for cleft palate after that point in gestation, other risks remain. These include gestational diabetes, gestational hypertension, osteoporosis in the mother, premature rupture of the membranes, and small-for-gestational-age infants.

Prednisone and methylprednisolone—the steroids rheumatologists utilize most often—don't cross the placenta efficiently, and hence are much less likely to cause fetal adverse effects than are dexamethasone or betamethasone.

Steroids that are administered to the mother make their way into breast milk only in low concentrations. If she's on less than 20 mg/day of prednisone, she can breastfeed normally. For women on higher doses, Dr. Bermas advises pumping and discarding the breast milk for the first 4 hours after a dose is taken.

Dr. Bermas emphasized that the key to successful treatment of rheumatologic disorders during pregnancy is a clear-eyed assessment of and accommodation to the patient's tolerance for risk—and the physician's, as well.

“There are some women who do not drink caffeinated beverages or take any medications, not even a Tylenol, and who will eat only organic foods while pregnant. There are others who are willing to tolerate some risk during pregnancy. And as clinicians, we have our own risk tolerances, too. For example, azathioprine is a medication that I feel comfortable using during pregnancy, but I have colleagues who won't because they wouldn't be able to sleep at night,” she explained.

The reason she prescribes azathioprine during pregnancy—despite its category D rating from the Food and Drug Administration, indicating “positive evidence of risk”—is that there's an enormous transplant literature showing no increase in congenital anomalies with in utero exposure to this drug.

Mycophenolate mofetil (CellCept) also has a category D rating. But unlike azathioprine, mycophenolate mofetil has no extensive and reassuring transplant literature. As a result, Dr. Bermas said that she avoids it in pregnancy and nursing.

Other rheumatologic medications to avoid in pregnancy are methotrexate, penicillamine, 6-mercaptopurine, and chlorambucil, she continued.

The use of tumor necrosis factor inhibitors during pregnancy is an extremely challenging question. Although at present the FDA rates them as category B (“no evidence of risk in humans”), that could very well change as a result of a reported association (J. Rheumatol. 2009;36:635-41) with VACTERL anomalies, which include vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities. On the other hand, several editorials and review articles have expressed the view that the risk of VACTERL anomaly after in utero exposure is overstated.

When lupus patients on antimalarials become pregnant, Dr. Bermas said she generally keeps them on the medication. She also allows patients to remain on antimalarials while nursing, which is consistent with the position of the American Academy of Pediatrics.

For mild cases of rheumatologic disease in pregnancy, Dr. Bermas reported that she relies on NSAIDs and/or prednisone at 5-10 mg/day. She halts the NSAID after the second trimester in order to avoid premature closure of a patent ductus arteriosus. For an inflammatory mild arthritis, she considers adding sulfasalazine.

She said she manages moderate disease with higher-dose steroids, azathioprine, or cyclosporine. For severe disease, Dr. Bermas reported that she turns to pulse steroids, azathioprine, cyclosporine, or intravenous immunoglobulin. In life-or-death situations, there are many case reports of cyclophosphamide being used successfully in the third trimester, a time by which most organogenesis is completed.

Dr. Bermas reported having no financial conflicts of interest.

“Corticosteroids have been my ace in the hole in treating many patients … [They] can get you out of a lot of trouble.'

Source DR. BERMAS

A significant number of men experience prenatal and postpartum depression, and the rate is marginally higher in the United States than in other countries, according to a meta-analysis of 43 studies.

The overall rate of paternal depression was 10.4%, with a U.S. rate of 14.1% vs. 8.2% in other countries. The study also reported maternal depression at a rate of 23.8%, with a moderate positive correlation between maternal and paternal depression.

The findings suggest that “more efforts should be made to improve screening and referral, particularly in light of the mounting evidence that early paternal depression may have substantial emotional, behavioral, and developmental effects on children,” noted James F. Paulson, Ph.D., and his colleague Sharnail D. Bazemore of the department of pediatrics at Eastern Virginia Medical School in Norfolk (JAMA 2010;303:1961-9). The correlation between paternal and maternal depression “also suggests a screening rubric – depression in one patient should prompt clinical attention to the other,” the investigators wrote.

The meta-analysis included studies from 16 countries and involved 28,004 new and expectant fathers aged 18 years or older.

A significant number of men experience prenatal and postpartum depression, and the rate is marginally higher in the United States than in other countries, according to a meta-analysis of 43 studies.

The overall rate of paternal depression was 10.4%, with a U.S. rate of 14.1% vs. 8.2% in other countries. The study also reported maternal depression at a rate of 23.8%, with a moderate positive correlation between maternal and paternal depression.

The findings suggest that “more efforts should be made to improve screening and referral, particularly in light of the mounting evidence that early paternal depression may have substantial emotional, behavioral, and developmental effects on children,” noted James F. Paulson, Ph.D., and his colleague Sharnail D. Bazemore of the department of pediatrics at Eastern Virginia Medical School in Norfolk (JAMA 2010;303:1961-9). The correlation between paternal and maternal depression “also suggests a screening rubric – depression in one patient should prompt clinical attention to the other,” the investigators wrote.

The meta-analysis included studies from 16 countries and involved 28,004 new and expectant fathers aged 18 years or older.

A significant number of men experience prenatal and postpartum depression, and the rate is marginally higher in the United States than in other countries, according to a meta-analysis of 43 studies.

The overall rate of paternal depression was 10.4%, with a U.S. rate of 14.1% vs. 8.2% in other countries. The study also reported maternal depression at a rate of 23.8%, with a moderate positive correlation between maternal and paternal depression.

The findings suggest that “more efforts should be made to improve screening and referral, particularly in light of the mounting evidence that early paternal depression may have substantial emotional, behavioral, and developmental effects on children,” noted James F. Paulson, Ph.D., and his colleague Sharnail D. Bazemore of the department of pediatrics at Eastern Virginia Medical School in Norfolk (JAMA 2010;303:1961-9). The correlation between paternal and maternal depression “also suggests a screening rubric – depression in one patient should prompt clinical attention to the other,” the investigators wrote.

The meta-analysis included studies from 16 countries and involved 28,004 new and expectant fathers aged 18 years or older.

Major Finding: Newborns in the DTaP group had substantially higher antibody concentrations than infants in the control group prior to the start of their primary DTaP series, and the differences were statistically significant.

Data Source: Prospective cohort study involving 70 women and their infants; some of the mothers received DTaP vaccine during pregnancy.

Disclosures: Dr. Hardy-Fairbanks said she had no conflicts of interest. The study was funded by Sanofi-Pasteur, maker of Daptacel DTaP vaccine.

VANCOUVER, B.C. – Infants born to women who receive diphtheria-tetanus-acellular pertussis vaccine during pregnancy have higher pertussis antibody levels during their first few months of life than infants born to unvaccinated women, Dr. Abbey Hardy-Fairbanks reported.

The levels are sufficient to protect infants against pertussis prior to their first diphtheria-tetanus-acellular pertussis (DTaP) shot at around 2 months, a period of “significant pertussis morbidity and mortality,” said Dr. Hardy-Fairbanks, an ob.gyn. at the University of Iowa, Iowa City.

“This is the first evidence to document that pertussis immunization during pregnancy is likely to be beneficial to infants when they are most vulnerable to pertussis disease.

Physicians “should consider vaccination of women during pregnancy with DTaP,” she said at the meeting.

In the prospective cohort study, 16 (23%) of 70 pregnant women received DTaP vaccine; 54 (77%) pregnant women selected as controls did not and had not been vaccinated for at least 2 years.

Four of the women (25%) in the DTaP group were vaccinated in the first trimester, eight (50%) in the second, and four (25%) in the third. Vaccination did not cause any adverse pregnancy outcomes.

Maternal blood and cord blood were collected at delivery.

Blood was also collected from children before and after their primary DTaP series and toddler booster doses at 12-18 months.

Blood samples were measured for pertussis antigens, including pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae, by enzyme-linked immunosorbent assay.

Newborns in the DTaP group had higher pertussis antibody concentrations than their mothers, “showing efficient placental transfer of antibodies to the infant,” Dr. Hardy-Fairbanks said.

They also had substantially higher concentrations than infants in the control group prior to the start of the primary DTaP series, and the differences were statistically significant.

However, at month 7, following completion of the DTaP series, infants born to vaccinated mothers had slightly lower antibody levels than infants in the control group.

The differences were not statistically significant, but “may represent some blunting of the infant immune response to the [vaccine],” Dr. Hardy-Fairbanks said.

By the time they got their toddler booster doses, however, antibody levels “were essentially equivalent” in the two groups, she said.

View on the News

Possible Blunted Immune Response?

Dr. Sarah Long thanked the study authors for their work. “Your findings are so very helpful. We don't have this kind of information.”

She was concerned, however, that infants born to vaccinated mothers mounted only a blunted immune response to their primary DTaP vaccine series, and wondered if responses would be blunted to other vaccines. The study's presenter said the question is currently being investigated, but so far that does not appear to be the case.

DR. LONG is the chief of the section of infectious diseases at St. Christopher's Hospital for Children in Philadelphia. She said she had no conflicts of interest.

Major Finding: Newborns in the DTaP group had substantially higher antibody concentrations than infants in the control group prior to the start of their primary DTaP series, and the differences were statistically significant.

Data Source: Prospective cohort study involving 70 women and their infants; some of the mothers received DTaP vaccine during pregnancy.

Disclosures: Dr. Hardy-Fairbanks said she had no conflicts of interest. The study was funded by Sanofi-Pasteur, maker of Daptacel DTaP vaccine.

VANCOUVER, B.C. – Infants born to women who receive diphtheria-tetanus-acellular pertussis vaccine during pregnancy have higher pertussis antibody levels during their first few months of life than infants born to unvaccinated women, Dr. Abbey Hardy-Fairbanks reported.

The levels are sufficient to protect infants against pertussis prior to their first diphtheria-tetanus-acellular pertussis (DTaP) shot at around 2 months, a period of “significant pertussis morbidity and mortality,” said Dr. Hardy-Fairbanks, an ob.gyn. at the University of Iowa, Iowa City.

“This is the first evidence to document that pertussis immunization during pregnancy is likely to be beneficial to infants when they are most vulnerable to pertussis disease.

Physicians “should consider vaccination of women during pregnancy with DTaP,” she said at the meeting.

In the prospective cohort study, 16 (23%) of 70 pregnant women received DTaP vaccine; 54 (77%) pregnant women selected as controls did not and had not been vaccinated for at least 2 years.

Four of the women (25%) in the DTaP group were vaccinated in the first trimester, eight (50%) in the second, and four (25%) in the third. Vaccination did not cause any adverse pregnancy outcomes.

Maternal blood and cord blood were collected at delivery.

Blood was also collected from children before and after their primary DTaP series and toddler booster doses at 12-18 months.

Blood samples were measured for pertussis antigens, including pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae, by enzyme-linked immunosorbent assay.

Newborns in the DTaP group had higher pertussis antibody concentrations than their mothers, “showing efficient placental transfer of antibodies to the infant,” Dr. Hardy-Fairbanks said.

They also had substantially higher concentrations than infants in the control group prior to the start of the primary DTaP series, and the differences were statistically significant.

However, at month 7, following completion of the DTaP series, infants born to vaccinated mothers had slightly lower antibody levels than infants in the control group.

The differences were not statistically significant, but “may represent some blunting of the infant immune response to the [vaccine],” Dr. Hardy-Fairbanks said.

By the time they got their toddler booster doses, however, antibody levels “were essentially equivalent” in the two groups, she said.

View on the News

Possible Blunted Immune Response?

Dr. Sarah Long thanked the study authors for their work. “Your findings are so very helpful. We don't have this kind of information.”

She was concerned, however, that infants born to vaccinated mothers mounted only a blunted immune response to their primary DTaP vaccine series, and wondered if responses would be blunted to other vaccines. The study's presenter said the question is currently being investigated, but so far that does not appear to be the case.

DR. LONG is the chief of the section of infectious diseases at St. Christopher's Hospital for Children in Philadelphia. She said she had no conflicts of interest.

Major Finding: Newborns in the DTaP group had substantially higher antibody concentrations than infants in the control group prior to the start of their primary DTaP series, and the differences were statistically significant.

Data Source: Prospective cohort study involving 70 women and their infants; some of the mothers received DTaP vaccine during pregnancy.

Disclosures: Dr. Hardy-Fairbanks said she had no conflicts of interest. The study was funded by Sanofi-Pasteur, maker of Daptacel DTaP vaccine.

VANCOUVER, B.C. – Infants born to women who receive diphtheria-tetanus-acellular pertussis vaccine during pregnancy have higher pertussis antibody levels during their first few months of life than infants born to unvaccinated women, Dr. Abbey Hardy-Fairbanks reported.

The levels are sufficient to protect infants against pertussis prior to their first diphtheria-tetanus-acellular pertussis (DTaP) shot at around 2 months, a period of “significant pertussis morbidity and mortality,” said Dr. Hardy-Fairbanks, an ob.gyn. at the University of Iowa, Iowa City.

“This is the first evidence to document that pertussis immunization during pregnancy is likely to be beneficial to infants when they are most vulnerable to pertussis disease.

Physicians “should consider vaccination of women during pregnancy with DTaP,” she said at the meeting.

In the prospective cohort study, 16 (23%) of 70 pregnant women received DTaP vaccine; 54 (77%) pregnant women selected as controls did not and had not been vaccinated for at least 2 years.

Four of the women (25%) in the DTaP group were vaccinated in the first trimester, eight (50%) in the second, and four (25%) in the third. Vaccination did not cause any adverse pregnancy outcomes.

Maternal blood and cord blood were collected at delivery.

Blood was also collected from children before and after their primary DTaP series and toddler booster doses at 12-18 months.

Blood samples were measured for pertussis antigens, including pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae, by enzyme-linked immunosorbent assay.

Newborns in the DTaP group had higher pertussis antibody concentrations than their mothers, “showing efficient placental transfer of antibodies to the infant,” Dr. Hardy-Fairbanks said.

They also had substantially higher concentrations than infants in the control group prior to the start of the primary DTaP series, and the differences were statistically significant.

However, at month 7, following completion of the DTaP series, infants born to vaccinated mothers had slightly lower antibody levels than infants in the control group.

The differences were not statistically significant, but “may represent some blunting of the infant immune response to the [vaccine],” Dr. Hardy-Fairbanks said.

By the time they got their toddler booster doses, however, antibody levels “were essentially equivalent” in the two groups, she said.

View on the News

Possible Blunted Immune Response?

Dr. Sarah Long thanked the study authors for their work. “Your findings are so very helpful. We don't have this kind of information.”

She was concerned, however, that infants born to vaccinated mothers mounted only a blunted immune response to their primary DTaP vaccine series, and wondered if responses would be blunted to other vaccines. The study's presenter said the question is currently being investigated, but so far that does not appear to be the case.

DR. LONG is the chief of the section of infectious diseases at St. Christopher's Hospital for Children in Philadelphia. She said she had no conflicts of interest.

Women who take over-the-counter painkillers during pregnancy have an increased risk of having sons born with undescended testes, according to a study that also incorporates rat models to show why this might be.

Using data from a birth cohort study of singleton sons born to 1,463 women in Finland and 834 in Denmark, all of whom either completed written questionnaires or telephone interviews or both, the researchers, led by Henrik Leffers, Ph.D., of Rigshospitalet in Copenhagen, found the risk of cryptorchidism to increase sevenfold in boys born to women who used more then one of three over-the-counter painkillers – aspirin (acetylsalicylic acid), acetaminophen (paracetamol), or ibuprofen – simultaneously during their pregnancies.

Exact doses of the painkillers were not recorded.

The findings, published online Nov. 8 in the journal Human Reproduction (doi:10.1093/humrep/deq323), also showed that any of these painkillers that were used for any duration during the second trimester more than doubled the risk of cryptorchidism, although the association for acetaminophen did not reach statistical significance.

The highest risk was observed, Dr. Leffers and his colleagues reported, among women who used more than one compound simultaneously for more than 2 weeks in the second trimester (adjusted odds ratio, 21.7 [1.83-258]).

A possible mechanism for this effect, Dr. Leffers and his colleagues hypothesized, was demonstrated by some of the study's coauthors, who found in a linked investigation that intrauterine exposure to acetaminophen, at three times the recommended dose for humans, led to a reduction in anogenital distance among fetal rats, and also reduced testosterone production by about half in fetal rat testes.

Aspirin was also tested in rats, but the results were not conclusive.

“A particular strength of this study is the use of two complementary rat models to support the contention that the association between analgesic use and cryptorchidism seen in our cohort study may result from a reduction in androgen production,” Dr. Leffers and his colleagues wrote.

Their study adds to findings published earlier this month (Epidemiology 2010;21:779-85) from a cohort of 47,000 boys born in Denmark, 980 of whom were identified in childhood as having cryptorchidism. That study, which also looked at acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy through telephone interviews and questionnaires with mothers, saw exposure to acetaminophen during both the first and second trimesters associated with increased cryptorchidism (hazard ratio, 1.33).

Acetaminophen exposure of more than 4 weeks between the 8th and 14th gestational weeks was associated with an HR of 1.38. However no association was found for either ibuprofen or aspirin.

Dr. Leffers and his colleagues' study found all but one of their statistically significant associations in the Danish part of their cohort, and speculated that differences in design of the Finnish and Danish cohort studies may have been partly responsible.

Although the Finnish questionnaire asked respondents to list only which medications were taken and when, the Danish telephone interviews asked the most pointed questions about over-the-counter and prescription pain medications, including which products were used in which weeks of pregnancy.

Although just more than a quarter (26%) of the Danish mothers who responded to the written questionnaire said that they had used mild analgesics, more than half (56%) of those interviewed by telephone said the same.

“These findings indicated that many mothers did not consider mild analgesics as medication and hence strongly underreported their use unless specifically asked. We therefore only included the data from the computer-assisted telephone interview from the Danish part of the study,” the investigators wrote.

In a press release accompanying the study, Dr. Leffers said that a “single paracetamol tablet (500 mg) contains more endocrine disruptor potency than the combined exposure to the 10 most prevalent of the currently known environmental endocrine disruptors during the whole pregnancy.”

Men who are born with cryptorchidism, the researchers noted, see an increased risk of having poor semen quality and testicular germ cell cancer.

Dr. Leffers and his colleagues' study was funded by European Commission and French government grants, the Villum Kann Rasmussen Foundation, and Novo Nordisk.

None of its authors declared conflicts of interest.

Women who take over-the-counter painkillers during pregnancy have an increased risk of having sons born with undescended testes, according to a study that also incorporates rat models to show why this might be.

Using data from a birth cohort study of singleton sons born to 1,463 women in Finland and 834 in Denmark, all of whom either completed written questionnaires or telephone interviews or both, the researchers, led by Henrik Leffers, Ph.D., of Rigshospitalet in Copenhagen, found the risk of cryptorchidism to increase sevenfold in boys born to women who used more then one of three over-the-counter painkillers – aspirin (acetylsalicylic acid), acetaminophen (paracetamol), or ibuprofen – simultaneously during their pregnancies.

Exact doses of the painkillers were not recorded.

The findings, published online Nov. 8 in the journal Human Reproduction (doi:10.1093/humrep/deq323), also showed that any of these painkillers that were used for any duration during the second trimester more than doubled the risk of cryptorchidism, although the association for acetaminophen did not reach statistical significance.

The highest risk was observed, Dr. Leffers and his colleagues reported, among women who used more than one compound simultaneously for more than 2 weeks in the second trimester (adjusted odds ratio, 21.7 [1.83-258]).

A possible mechanism for this effect, Dr. Leffers and his colleagues hypothesized, was demonstrated by some of the study's coauthors, who found in a linked investigation that intrauterine exposure to acetaminophen, at three times the recommended dose for humans, led to a reduction in anogenital distance among fetal rats, and also reduced testosterone production by about half in fetal rat testes.

Aspirin was also tested in rats, but the results were not conclusive.

“A particular strength of this study is the use of two complementary rat models to support the contention that the association between analgesic use and cryptorchidism seen in our cohort study may result from a reduction in androgen production,” Dr. Leffers and his colleagues wrote.

Their study adds to findings published earlier this month (Epidemiology 2010;21:779-85) from a cohort of 47,000 boys born in Denmark, 980 of whom were identified in childhood as having cryptorchidism. That study, which also looked at acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy through telephone interviews and questionnaires with mothers, saw exposure to acetaminophen during both the first and second trimesters associated with increased cryptorchidism (hazard ratio, 1.33).

Acetaminophen exposure of more than 4 weeks between the 8th and 14th gestational weeks was associated with an HR of 1.38. However no association was found for either ibuprofen or aspirin.

Dr. Leffers and his colleagues' study found all but one of their statistically significant associations in the Danish part of their cohort, and speculated that differences in design of the Finnish and Danish cohort studies may have been partly responsible.

Although the Finnish questionnaire asked respondents to list only which medications were taken and when, the Danish telephone interviews asked the most pointed questions about over-the-counter and prescription pain medications, including which products were used in which weeks of pregnancy.

Although just more than a quarter (26%) of the Danish mothers who responded to the written questionnaire said that they had used mild analgesics, more than half (56%) of those interviewed by telephone said the same.

“These findings indicated that many mothers did not consider mild analgesics as medication and hence strongly underreported their use unless specifically asked. We therefore only included the data from the computer-assisted telephone interview from the Danish part of the study,” the investigators wrote.

In a press release accompanying the study, Dr. Leffers said that a “single paracetamol tablet (500 mg) contains more endocrine disruptor potency than the combined exposure to the 10 most prevalent of the currently known environmental endocrine disruptors during the whole pregnancy.”

Men who are born with cryptorchidism, the researchers noted, see an increased risk of having poor semen quality and testicular germ cell cancer.

Dr. Leffers and his colleagues' study was funded by European Commission and French government grants, the Villum Kann Rasmussen Foundation, and Novo Nordisk.

None of its authors declared conflicts of interest.

Women who take over-the-counter painkillers during pregnancy have an increased risk of having sons born with undescended testes, according to a study that also incorporates rat models to show why this might be.

Using data from a birth cohort study of singleton sons born to 1,463 women in Finland and 834 in Denmark, all of whom either completed written questionnaires or telephone interviews or both, the researchers, led by Henrik Leffers, Ph.D., of Rigshospitalet in Copenhagen, found the risk of cryptorchidism to increase sevenfold in boys born to women who used more then one of three over-the-counter painkillers – aspirin (acetylsalicylic acid), acetaminophen (paracetamol), or ibuprofen – simultaneously during their pregnancies.

Exact doses of the painkillers were not recorded.

The findings, published online Nov. 8 in the journal Human Reproduction (doi:10.1093/humrep/deq323), also showed that any of these painkillers that were used for any duration during the second trimester more than doubled the risk of cryptorchidism, although the association for acetaminophen did not reach statistical significance.

The highest risk was observed, Dr. Leffers and his colleagues reported, among women who used more than one compound simultaneously for more than 2 weeks in the second trimester (adjusted odds ratio, 21.7 [1.83-258]).

A possible mechanism for this effect, Dr. Leffers and his colleagues hypothesized, was demonstrated by some of the study's coauthors, who found in a linked investigation that intrauterine exposure to acetaminophen, at three times the recommended dose for humans, led to a reduction in anogenital distance among fetal rats, and also reduced testosterone production by about half in fetal rat testes.

Aspirin was also tested in rats, but the results were not conclusive.

“A particular strength of this study is the use of two complementary rat models to support the contention that the association between analgesic use and cryptorchidism seen in our cohort study may result from a reduction in androgen production,” Dr. Leffers and his colleagues wrote.

Their study adds to findings published earlier this month (Epidemiology 2010;21:779-85) from a cohort of 47,000 boys born in Denmark, 980 of whom were identified in childhood as having cryptorchidism. That study, which also looked at acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy through telephone interviews and questionnaires with mothers, saw exposure to acetaminophen during both the first and second trimesters associated with increased cryptorchidism (hazard ratio, 1.33).

Acetaminophen exposure of more than 4 weeks between the 8th and 14th gestational weeks was associated with an HR of 1.38. However no association was found for either ibuprofen or aspirin.

Dr. Leffers and his colleagues' study found all but one of their statistically significant associations in the Danish part of their cohort, and speculated that differences in design of the Finnish and Danish cohort studies may have been partly responsible.

Although the Finnish questionnaire asked respondents to list only which medications were taken and when, the Danish telephone interviews asked the most pointed questions about over-the-counter and prescription pain medications, including which products were used in which weeks of pregnancy.

Although just more than a quarter (26%) of the Danish mothers who responded to the written questionnaire said that they had used mild analgesics, more than half (56%) of those interviewed by telephone said the same.

“These findings indicated that many mothers did not consider mild analgesics as medication and hence strongly underreported their use unless specifically asked. We therefore only included the data from the computer-assisted telephone interview from the Danish part of the study,” the investigators wrote.

In a press release accompanying the study, Dr. Leffers said that a “single paracetamol tablet (500 mg) contains more endocrine disruptor potency than the combined exposure to the 10 most prevalent of the currently known environmental endocrine disruptors during the whole pregnancy.”

Men who are born with cryptorchidism, the researchers noted, see an increased risk of having poor semen quality and testicular germ cell cancer.

Dr. Leffers and his colleagues' study was funded by European Commission and French government grants, the Villum Kann Rasmussen Foundation, and Novo Nordisk.

None of its authors declared conflicts of interest.

NEW ORLEANS – Pregnant women who used proton pump inhibitors for gastroesophageal reflux during the first trimester of pregnancy were more than twice as likely to have babies with cardiac defects than were pregnant women who did not use PPIs, based on a retrospective study of 200,000 women.

Previous data have indicated a nonsignificant trend toward an association between use of proton pump inhibitors (PPIs) early in pregnancy and cardiac malformations, Dr. Andrew D. Rhim of the University of Pennsylvania in Philadelphia said in his presentation.

“Before this study, there were very limited human data [on risk], and this study suggests a possible increased risk of cardiovascular defects,” Dr. Jennifer Niebyl of the University of Iowa, Iowa City, said in an interview. A prospective study is needed to confirm these results, which are hampered by uncertainties surrounding the trimester of exposure and possible selection bias.

Dr. Niebyl and her colleagues conducted a study of 3,458 women that suggested metoclopramide may be a safe option for pregnant women (N. Engl. J. Med. 2009;360:2528-35). She advised that pregnant women avoid PPIs during the first trimester.

From a database of 208,951 pregnancies, Dr. Rhim and his colleagues identified 2,445 cases of cardiac malformations in newborns and compared them with 19,530 matched controls. All the newborns were registered between 2000 and 2008 in The Health Improvement Network, a database of information collected by general practitioners in the United Kingdom. “We found 130 instances of a PPI being prescribed within the first trimester” in the women who gave birth to infants with cardiac birth defects, Dr. Rhim said. After adjustment for multiple variables including maternal BMI, smoking status, alcohol use, and use of other medications, the risk for cardiac birth defects remained significant (odds ratio, 2.14). A history of cardiac malformations or diabetes in the mother was associated with a significantly increased risk of a cardiac defect in the baby.

The researchers identified septal, left ventricular, and right ventricular defects.

Dr. Rhim said that he had no financial conflicts to disclose.

View on the News

Timing Is Very Important

Retrospective case-control studies can show associations, but they cannot determine if the associations are causal. Moreover, such studies have major limitations, including selection bias, recall bias and timing of exposures, Timing is very important. For example, closure of the ventricular septum occurs by 6 weeks post conception, so an exposure that causes a ventricular septal defect (VSD) must occur before 6 weeks.

Consider the animal reproduction data included by manufacturers in package inserts. None of the six PPIs in the United States (dexlansoprazole [Dexilant], esomeprazole [Nexium], lansoprazole [Prevacid], omeprazole [Prilosec], pantoprazole [Protonix], and rabeprazole [Aciphex]) cause structural defects in animals. This is important: With only two exceptions, all known human teratogens also are teratogenic in animals.

I know of no studies that have shown a significant association between PPIs and cardiac defects. Atrial septal defects and VSDs are among the most common cardiac defects. VSDs are among the most common birth defects.

GERALD BRIGGS is clinical professor of pharmacy at the University of California, San Francisco.

NEW ORLEANS – Pregnant women who used proton pump inhibitors for gastroesophageal reflux during the first trimester of pregnancy were more than twice as likely to have babies with cardiac defects than were pregnant women who did not use PPIs, based on a retrospective study of 200,000 women.

Previous data have indicated a nonsignificant trend toward an association between use of proton pump inhibitors (PPIs) early in pregnancy and cardiac malformations, Dr. Andrew D. Rhim of the University of Pennsylvania in Philadelphia said in his presentation.

“Before this study, there were very limited human data [on risk], and this study suggests a possible increased risk of cardiovascular defects,” Dr. Jennifer Niebyl of the University of Iowa, Iowa City, said in an interview. A prospective study is needed to confirm these results, which are hampered by uncertainties surrounding the trimester of exposure and possible selection bias.

Dr. Niebyl and her colleagues conducted a study of 3,458 women that suggested metoclopramide may be a safe option for pregnant women (N. Engl. J. Med. 2009;360:2528-35). She advised that pregnant women avoid PPIs during the first trimester.

From a database of 208,951 pregnancies, Dr. Rhim and his colleagues identified 2,445 cases of cardiac malformations in newborns and compared them with 19,530 matched controls. All the newborns were registered between 2000 and 2008 in The Health Improvement Network, a database of information collected by general practitioners in the United Kingdom. “We found 130 instances of a PPI being prescribed within the first trimester” in the women who gave birth to infants with cardiac birth defects, Dr. Rhim said. After adjustment for multiple variables including maternal BMI, smoking status, alcohol use, and use of other medications, the risk for cardiac birth defects remained significant (odds ratio, 2.14). A history of cardiac malformations or diabetes in the mother was associated with a significantly increased risk of a cardiac defect in the baby.

The researchers identified septal, left ventricular, and right ventricular defects.

Dr. Rhim said that he had no financial conflicts to disclose.

View on the News

Timing Is Very Important

Retrospective case-control studies can show associations, but they cannot determine if the associations are causal. Moreover, such studies have major limitations, including selection bias, recall bias and timing of exposures, Timing is very important. For example, closure of the ventricular septum occurs by 6 weeks post conception, so an exposure that causes a ventricular septal defect (VSD) must occur before 6 weeks.

Consider the animal reproduction data included by manufacturers in package inserts. None of the six PPIs in the United States (dexlansoprazole [Dexilant], esomeprazole [Nexium], lansoprazole [Prevacid], omeprazole [Prilosec], pantoprazole [Protonix], and rabeprazole [Aciphex]) cause structural defects in animals. This is important: With only two exceptions, all known human teratogens also are teratogenic in animals.

I know of no studies that have shown a significant association between PPIs and cardiac defects. Atrial septal defects and VSDs are among the most common cardiac defects. VSDs are among the most common birth defects.

GERALD BRIGGS is clinical professor of pharmacy at the University of California, San Francisco.

NEW ORLEANS – Pregnant women who used proton pump inhibitors for gastroesophageal reflux during the first trimester of pregnancy were more than twice as likely to have babies with cardiac defects than were pregnant women who did not use PPIs, based on a retrospective study of 200,000 women.

Previous data have indicated a nonsignificant trend toward an association between use of proton pump inhibitors (PPIs) early in pregnancy and cardiac malformations, Dr. Andrew D. Rhim of the University of Pennsylvania in Philadelphia said in his presentation.

“Before this study, there were very limited human data [on risk], and this study suggests a possible increased risk of cardiovascular defects,” Dr. Jennifer Niebyl of the University of Iowa, Iowa City, said in an interview. A prospective study is needed to confirm these results, which are hampered by uncertainties surrounding the trimester of exposure and possible selection bias.

Dr. Niebyl and her colleagues conducted a study of 3,458 women that suggested metoclopramide may be a safe option for pregnant women (N. Engl. J. Med. 2009;360:2528-35). She advised that pregnant women avoid PPIs during the first trimester.

From a database of 208,951 pregnancies, Dr. Rhim and his colleagues identified 2,445 cases of cardiac malformations in newborns and compared them with 19,530 matched controls. All the newborns were registered between 2000 and 2008 in The Health Improvement Network, a database of information collected by general practitioners in the United Kingdom. “We found 130 instances of a PPI being prescribed within the first trimester” in the women who gave birth to infants with cardiac birth defects, Dr. Rhim said. After adjustment for multiple variables including maternal BMI, smoking status, alcohol use, and use of other medications, the risk for cardiac birth defects remained significant (odds ratio, 2.14). A history of cardiac malformations or diabetes in the mother was associated with a significantly increased risk of a cardiac defect in the baby.

The researchers identified septal, left ventricular, and right ventricular defects.

Dr. Rhim said that he had no financial conflicts to disclose.

View on the News

Timing Is Very Important

Retrospective case-control studies can show associations, but they cannot determine if the associations are causal. Moreover, such studies have major limitations, including selection bias, recall bias and timing of exposures, Timing is very important. For example, closure of the ventricular septum occurs by 6 weeks post conception, so an exposure that causes a ventricular septal defect (VSD) must occur before 6 weeks.

Consider the animal reproduction data included by manufacturers in package inserts. None of the six PPIs in the United States (dexlansoprazole [Dexilant], esomeprazole [Nexium], lansoprazole [Prevacid], omeprazole [Prilosec], pantoprazole [Protonix], and rabeprazole [Aciphex]) cause structural defects in animals. This is important: With only two exceptions, all known human teratogens also are teratogenic in animals.

I know of no studies that have shown a significant association between PPIs and cardiac defects. Atrial septal defects and VSDs are among the most common cardiac defects. VSDs are among the most common birth defects.

GERALD BRIGGS is clinical professor of pharmacy at the University of California, San Francisco.

Major Finding: A history of one or more abortions was associated with a twofold increase in preterm delivery at less than 24 weeks' gestation.

Data Source: A study of 3,138 women who had one or more therapeutic abortions who underwent a subsequent delivery of a live singleton or multiples and 14,778 women who had no history of abortion and who gave birth at the hospital during the same period.

Disclosures: None was reported.

MONTREAL – Women with a history of one or more therapeutic abortions have double the risk of preterm delivery before 24 weeks' gestation in a subsequent pregnancy, compared with those with no abortion history, a study by researchers from McGill University in Montreal has shown.

“The implications are that abortions can lead to cervical insufficiency, and that public health efforts should aim at prevention through early counseling and provision of effective contraception for all women,” said the principal investigator, Dr. Haim Abenhaim, obstetrician/gynecologist at Montreal's SMBD Jewish General Hospital, which is part of McGill University.

The retrospective study, presented by Dr. Ghislain Hardy at the meeting, looked at all women who had undergone an induced abortion and subsequent delivery of a live singleton or multiples birth at a single, tertiary care institution between 2001 and 2006.

A total of 2,276 women had undergone one abortion, and 862 had undergone two or more. These women were compared with 14,778 women who had no history of abortion and who gave birth at the hospital during the same period.

Most of the therapeutic abortions [TABs] were first-trimester dilation and curettage, Dr. Abenhaim said in an interview. “For a therapeutic abortion (voluntary, for a normal pregnancy), the most common approach is a D&C [that is, surgical], while a medical approach is the more common for an arrested pregnancy.”

After adjustment for age, smoking, alcohol consumption, body mass index, marital status, and education, the investigators found that a history of one or more abortions was associated with a twofold increase in preterm delivery at less than 24 weeks. In addition, women with a history of abortion were more likely to require tocolysis – and this became statistically significant with two or more abortions (odds ratio, 1.42). Dr. Abenhaim did not present absolute numbers and did not respond to requests to acquire this information.

“The association between therapeutic abortions and prematurity has been seen before; however, our study was different in that it tried to examine the relationship between TABs and the timing of prematurity,” explained Dr. Abenhaim. “Prematurity caused by a cervical insufficiency is believed to occur earlier than prematurity which is considered idiopathic or infectious. Our results suggest that the effect of TABs is more consistent with early/cervical insufficiency–type preterm births.”

The findings are potentially important, said Dr. Anthony Armson, who chaired the session in which the study was presented. However, they should be interpreted with caution, especially since the study has not yet been published, said the professor and head of obstetrics and gynecology at Dalhousie University in Halifax, N.S.

“Certainly there has been evidence to support [the risk of] two or more therapeutic abortions in the first trimester, or any in the second-trimester – but that observation has not always been supported,” he said in an interview. “A number of investigators in the '80s and '90s, including myself, tried to come up with a risk-scoring algorithm to establish what factors were important in preterm birth. But in the vast majority, one therapeutic abortion did not come up as a risk factor.”

Major Finding: A history of one or more abortions was associated with a twofold increase in preterm delivery at less than 24 weeks' gestation.

Data Source: A study of 3,138 women who had one or more therapeutic abortions who underwent a subsequent delivery of a live singleton or multiples and 14,778 women who had no history of abortion and who gave birth at the hospital during the same period.

Disclosures: None was reported.

MONTREAL – Women with a history of one or more therapeutic abortions have double the risk of preterm delivery before 24 weeks' gestation in a subsequent pregnancy, compared with those with no abortion history, a study by researchers from McGill University in Montreal has shown.

“The implications are that abortions can lead to cervical insufficiency, and that public health efforts should aim at prevention through early counseling and provision of effective contraception for all women,” said the principal investigator, Dr. Haim Abenhaim, obstetrician/gynecologist at Montreal's SMBD Jewish General Hospital, which is part of McGill University.

The retrospective study, presented by Dr. Ghislain Hardy at the meeting, looked at all women who had undergone an induced abortion and subsequent delivery of a live singleton or multiples birth at a single, tertiary care institution between 2001 and 2006.

A total of 2,276 women had undergone one abortion, and 862 had undergone two or more. These women were compared with 14,778 women who had no history of abortion and who gave birth at the hospital during the same period.

Most of the therapeutic abortions [TABs] were first-trimester dilation and curettage, Dr. Abenhaim said in an interview. “For a therapeutic abortion (voluntary, for a normal pregnancy), the most common approach is a D&C [that is, surgical], while a medical approach is the more common for an arrested pregnancy.”

After adjustment for age, smoking, alcohol consumption, body mass index, marital status, and education, the investigators found that a history of one or more abortions was associated with a twofold increase in preterm delivery at less than 24 weeks. In addition, women with a history of abortion were more likely to require tocolysis – and this became statistically significant with two or more abortions (odds ratio, 1.42). Dr. Abenhaim did not present absolute numbers and did not respond to requests to acquire this information.

“The association between therapeutic abortions and prematurity has been seen before; however, our study was different in that it tried to examine the relationship between TABs and the timing of prematurity,” explained Dr. Abenhaim. “Prematurity caused by a cervical insufficiency is believed to occur earlier than prematurity which is considered idiopathic or infectious. Our results suggest that the effect of TABs is more consistent with early/cervical insufficiency–type preterm births.”

The findings are potentially important, said Dr. Anthony Armson, who chaired the session in which the study was presented. However, they should be interpreted with caution, especially since the study has not yet been published, said the professor and head of obstetrics and gynecology at Dalhousie University in Halifax, N.S.

“Certainly there has been evidence to support [the risk of] two or more therapeutic abortions in the first trimester, or any in the second-trimester – but that observation has not always been supported,” he said in an interview. “A number of investigators in the '80s and '90s, including myself, tried to come up with a risk-scoring algorithm to establish what factors were important in preterm birth. But in the vast majority, one therapeutic abortion did not come up as a risk factor.”

Major Finding: A history of one or more abortions was associated with a twofold increase in preterm delivery at less than 24 weeks' gestation.

Data Source: A study of 3,138 women who had one or more therapeutic abortions who underwent a subsequent delivery of a live singleton or multiples and 14,778 women who had no history of abortion and who gave birth at the hospital during the same period.

Disclosures: None was reported.

MONTREAL – Women with a history of one or more therapeutic abortions have double the risk of preterm delivery before 24 weeks' gestation in a subsequent pregnancy, compared with those with no abortion history, a study by researchers from McGill University in Montreal has shown.

“The implications are that abortions can lead to cervical insufficiency, and that public health efforts should aim at prevention through early counseling and provision of effective contraception for all women,” said the principal investigator, Dr. Haim Abenhaim, obstetrician/gynecologist at Montreal's SMBD Jewish General Hospital, which is part of McGill University.

The retrospective study, presented by Dr. Ghislain Hardy at the meeting, looked at all women who had undergone an induced abortion and subsequent delivery of a live singleton or multiples birth at a single, tertiary care institution between 2001 and 2006.

A total of 2,276 women had undergone one abortion, and 862 had undergone two or more. These women were compared with 14,778 women who had no history of abortion and who gave birth at the hospital during the same period.

Most of the therapeutic abortions [TABs] were first-trimester dilation and curettage, Dr. Abenhaim said in an interview. “For a therapeutic abortion (voluntary, for a normal pregnancy), the most common approach is a D&C [that is, surgical], while a medical approach is the more common for an arrested pregnancy.”

After adjustment for age, smoking, alcohol consumption, body mass index, marital status, and education, the investigators found that a history of one or more abortions was associated with a twofold increase in preterm delivery at less than 24 weeks. In addition, women with a history of abortion were more likely to require tocolysis – and this became statistically significant with two or more abortions (odds ratio, 1.42). Dr. Abenhaim did not present absolute numbers and did not respond to requests to acquire this information.

“The association between therapeutic abortions and prematurity has been seen before; however, our study was different in that it tried to examine the relationship between TABs and the timing of prematurity,” explained Dr. Abenhaim. “Prematurity caused by a cervical insufficiency is believed to occur earlier than prematurity which is considered idiopathic or infectious. Our results suggest that the effect of TABs is more consistent with early/cervical insufficiency–type preterm births.”

The findings are potentially important, said Dr. Anthony Armson, who chaired the session in which the study was presented. However, they should be interpreted with caution, especially since the study has not yet been published, said the professor and head of obstetrics and gynecology at Dalhousie University in Halifax, N.S.

“Certainly there has been evidence to support [the risk of] two or more therapeutic abortions in the first trimester, or any in the second-trimester – but that observation has not always been supported,” he said in an interview. “A number of investigators in the '80s and '90s, including myself, tried to come up with a risk-scoring algorithm to establish what factors were important in preterm birth. But in the vast majority, one therapeutic abortion did not come up as a risk factor.”

CASE: Risky decision to let labor continue

The baby was born blue and limp, after a long labor complicated by maternal fever and a prolonged fetal heart rate deceleration.

Earlier, just before the mother was raced to the OR for emergency cesarean delivery, the fetal heart rate had increased sufficiently for the OB to decide to permit labor to continue— the goal being rapid vaginal delivery.

In hindsight, that decision appears to have been potentially fateful for this newborn: Apgar scores were 1 at 5 minutes and 3 at 10 minutes. Umbilical artery pH was 6.98; base deficit, –13 mmol/L. The pediatricians made a preliminary diagnosis of hypoxic-ischemic injury and recommended whole-body cooling of the newborn to limit neural damage.

The frightened parents prayed the treatment would work. Later, recalling news reports that they had read about spinal cord-injured football players and survivors of cardiac arrest who received therapeutic cooling with apparent success, they grew more optimistic about the potential benefit of this treatment for their baby.

In animal models of hypoxic-ischemic neural injury, reducing core body temperature minimizes long-term neural consequences of the injury. Experiments have demonstrated that the optimal course is to induce hypothermia immediately after the neural injury, but initiating hypothermia even as long as 6 hours after injury has a protective effect.

Reducing core temperature appears to limit neural injury by decreasing oxygen requirements and suppressing the accumulation of harmful cytotoxic amino acids, cytokines, and free radicals. In contrast to the beneficial effect of hypothermia, raising body temperature by only 1°C or 2°C in experimental animals that have undergone an isolated hypoxic-ischemic event makes neural damage worse.

Clinical trials in newborns

The beneficial effect of whole-body cooling for newborns who have hypoxic-ischemic encephalopathy has been reported in several randomized clinical trials.

In a multicenter trial, supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, 208 newborns in severe acidosis at birth were randomized to whole-body cooling or usual care.¹ Whole-body cooling, initiated within 6 hours of birth, was achieved by:

• placing subjects on a cooling blanket precooled to 5°C
• inserting an esophageal temperature probe
• adjusting the temperature of the cooling blanket to achieve an esophageal temperature of 33.5°C for 72 hours
• slow rewarming.

Abdominal-wall skin temperature was also monitored in these newborns.

Subjects in the usual care group were nursed in an incubator, with the radiant heat element adjusted to maintain skin temperature of 36.5°C to 37°C.

Investigators determined that the composite end-point of risk of death or disability at 20 months of life was significantly reduced by whole-body cooling (relative risk, 0.72; 95% confidence interval [CI], 0.54–0.95; P=.01).

Death occurred in 24% of subjects in the hypothermia group and in 37% of subjects in the usual care group (risk ratio, 0.68; 95% CI, 0.44–1.05; P=.08). The rate of cerebral palsy was 19% in the hypothermia group and 30% in the usual care group (risk ratio, 0.68; 95% CI, 0.38–1.22; P=.20).

The rate of blindness was 7% in the hypothermia group and 14% in usual care group. The rate of hearing impairment was 4% and 6% percent (P - not significant).¹

In a second clinical trial, the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial of whole-body cooling, 325 newborns with hypoxic-ischemic encephalopathy were randomized to whole-body cooling or usual care.² Whole-body cooling was achieved by nursing the infant in an incubator on a cooling blanket set at 25°C to 30°C, with the goal of maintaining a rectal temperature in the newborn of 33°C to 34°C. In this group, the heat element in the incubator was turned off.

Newborns assigned to the usual care group were nursed in an incubator with the heat element turned on and set to maintain a rectal temperature of 37°C.

The rate of death was similar in the two groups, and the rate of severe neurodevelopmental disability in each of the groups was not significantly different. Among surviving infants, however, whole-body cooling was associated with a higher rate of intact neurologic function and a diminished risk of cerebral palsy (compared to what was seen in the usual-care group). Among surviving newborns, cerebral palsy occurred in 28% of those treated with whole-body cooling and in 41% of those receiving usual care (relative risk 0.67; 95% CI, 0.47–0.96; P=.03).

No major adverse effects were observed with whole-body cooling, when compare d against usual care. A 2007 meta-analysis of four trials of therapeutic hypothermia in newborns reported a significant reduction in the composite endpoint of death or in moderate or severe neurodevelopmental disability (relative risk 0.76; 95% CI, 0.65–0.88). The number that needed to be treated to prevent one endpoint event was 6 (95% CI, 4–14).³

Note that some pediatricians remain cautious about using therapeutic hypothermia, because long-term data on the safety and efficacy of the practice have not been reported.

Impact on your practice

For decades, newborns in neonatal intensive care units received their care in warm incubators designed to maintain a body temperature of approximately 37°C. Could the standard practice of warming newborns have contributed to neurologic problems in those who suffered hypoxic-ischemic injury?

Whole-body cooling appears to reduce the rate of cerebral palsy in newborns after hypoxic-ischemic injury. For OBs, this treatment could significantly reduce their exposure to litigation that is based on a theory of hypoxic-ischemic birth injury—by reducing the number of surviving infants who have cerebral palsy.

Does your nursery have a protocol for rapidly instituting therapeutic cooling?

How does the partial pressure of arterial oxygen (PaO₂) in a newborn compare with that of an adult breathing ambient air near the summit of Mount Everest?
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CASE: Risky decision to let labor continue

The baby was born blue and limp, after a long labor complicated by maternal fever and a prolonged fetal heart rate deceleration.

Earlier, just before the mother was raced to the OR for emergency cesarean delivery, the fetal heart rate had increased sufficiently for the OB to decide to permit labor to continue— the goal being rapid vaginal delivery.

In hindsight, that decision appears to have been potentially fateful for this newborn: Apgar scores were 1 at 5 minutes and 3 at 10 minutes. Umbilical artery pH was 6.98; base deficit, –13 mmol/L. The pediatricians made a preliminary diagnosis of hypoxic-ischemic injury and recommended whole-body cooling of the newborn to limit neural damage.

The frightened parents prayed the treatment would work. Later, recalling news reports that they had read about spinal cord-injured football players and survivors of cardiac arrest who received therapeutic cooling with apparent success, they grew more optimistic about the potential benefit of this treatment for their baby.

In animal models of hypoxic-ischemic neural injury, reducing core body temperature minimizes long-term neural consequences of the injury. Experiments have demonstrated that the optimal course is to induce hypothermia immediately after the neural injury, but initiating hypothermia even as long as 6 hours after injury has a protective effect.

Reducing core temperature appears to limit neural injury by decreasing oxygen requirements and suppressing the accumulation of harmful cytotoxic amino acids, cytokines, and free radicals. In contrast to the beneficial effect of hypothermia, raising body temperature by only 1°C or 2°C in experimental animals that have undergone an isolated hypoxic-ischemic event makes neural damage worse.

Clinical trials in newborns

The beneficial effect of whole-body cooling for newborns who have hypoxic-ischemic encephalopathy has been reported in several randomized clinical trials.

In a multicenter trial, supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, 208 newborns in severe acidosis at birth were randomized to whole-body cooling or usual care.¹ Whole-body cooling, initiated within 6 hours of birth, was achieved by:

• placing subjects on a cooling blanket precooled to 5°C
• inserting an esophageal temperature probe
• adjusting the temperature of the cooling blanket to achieve an esophageal temperature of 33.5°C for 72 hours
• slow rewarming.

Abdominal-wall skin temperature was also monitored in these newborns.

Subjects in the usual care group were nursed in an incubator, with the radiant heat element adjusted to maintain skin temperature of 36.5°C to 37°C.

Investigators determined that the composite end-point of risk of death or disability at 20 months of life was significantly reduced by whole-body cooling (relative risk, 0.72; 95% confidence interval [CI], 0.54–0.95; P=.01).

Death occurred in 24% of subjects in the hypothermia group and in 37% of subjects in the usual care group (risk ratio, 0.68; 95% CI, 0.44–1.05; P=.08). The rate of cerebral palsy was 19% in the hypothermia group and 30% in the usual care group (risk ratio, 0.68; 95% CI, 0.38–1.22; P=.20).

The rate of blindness was 7% in the hypothermia group and 14% in usual care group. The rate of hearing impairment was 4% and 6% percent (P - not significant).¹

In a second clinical trial, the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial of whole-body cooling, 325 newborns with hypoxic-ischemic encephalopathy were randomized to whole-body cooling or usual care.² Whole-body cooling was achieved by nursing the infant in an incubator on a cooling blanket set at 25°C to 30°C, with the goal of maintaining a rectal temperature in the newborn of 33°C to 34°C. In this group, the heat element in the incubator was turned off.

Newborns assigned to the usual care group were nursed in an incubator with the heat element turned on and set to maintain a rectal temperature of 37°C.

The rate of death was similar in the two groups, and the rate of severe neurodevelopmental disability in each of the groups was not significantly different. Among surviving infants, however, whole-body cooling was associated with a higher rate of intact neurologic function and a diminished risk of cerebral palsy (compared to what was seen in the usual-care group). Among surviving newborns, cerebral palsy occurred in 28% of those treated with whole-body cooling and in 41% of those receiving usual care (relative risk 0.67; 95% CI, 0.47–0.96; P=.03).

No major adverse effects were observed with whole-body cooling, when compare d against usual care. A 2007 meta-analysis of four trials of therapeutic hypothermia in newborns reported a significant reduction in the composite endpoint of death or in moderate or severe neurodevelopmental disability (relative risk 0.76; 95% CI, 0.65–0.88). The number that needed to be treated to prevent one endpoint event was 6 (95% CI, 4–14).³

Note that some pediatricians remain cautious about using therapeutic hypothermia, because long-term data on the safety and efficacy of the practice have not been reported.

Impact on your practice

For decades, newborns in neonatal intensive care units received their care in warm incubators designed to maintain a body temperature of approximately 37°C. Could the standard practice of warming newborns have contributed to neurologic problems in those who suffered hypoxic-ischemic injury?

Whole-body cooling appears to reduce the rate of cerebral palsy in newborns after hypoxic-ischemic injury. For OBs, this treatment could significantly reduce their exposure to litigation that is based on a theory of hypoxic-ischemic birth injury—by reducing the number of surviving infants who have cerebral palsy.

Does your nursery have a protocol for rapidly instituting therapeutic cooling?

How does the partial pressure of arterial oxygen (PaO₂) in a newborn compare with that of an adult breathing ambient air near the summit of Mount Everest?
Take the INSTANT QUIZ.

We want to hear from you! Tell us what you think.

CASE: Risky decision to let labor continue

The baby was born blue and limp, after a long labor complicated by maternal fever and a prolonged fetal heart rate deceleration.

Earlier, just before the mother was raced to the OR for emergency cesarean delivery, the fetal heart rate had increased sufficiently for the OB to decide to permit labor to continue— the goal being rapid vaginal delivery.

In hindsight, that decision appears to have been potentially fateful for this newborn: Apgar scores were 1 at 5 minutes and 3 at 10 minutes. Umbilical artery pH was 6.98; base deficit, –13 mmol/L. The pediatricians made a preliminary diagnosis of hypoxic-ischemic injury and recommended whole-body cooling of the newborn to limit neural damage.

The frightened parents prayed the treatment would work. Later, recalling news reports that they had read about spinal cord-injured football players and survivors of cardiac arrest who received therapeutic cooling with apparent success, they grew more optimistic about the potential benefit of this treatment for their baby.

In animal models of hypoxic-ischemic neural injury, reducing core body temperature minimizes long-term neural consequences of the injury. Experiments have demonstrated that the optimal course is to induce hypothermia immediately after the neural injury, but initiating hypothermia even as long as 6 hours after injury has a protective effect.

Reducing core temperature appears to limit neural injury by decreasing oxygen requirements and suppressing the accumulation of harmful cytotoxic amino acids, cytokines, and free radicals. In contrast to the beneficial effect of hypothermia, raising body temperature by only 1°C or 2°C in experimental animals that have undergone an isolated hypoxic-ischemic event makes neural damage worse.

Clinical trials in newborns

The beneficial effect of whole-body cooling for newborns who have hypoxic-ischemic encephalopathy has been reported in several randomized clinical trials.

In a multicenter trial, supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, 208 newborns in severe acidosis at birth were randomized to whole-body cooling or usual care.¹ Whole-body cooling, initiated within 6 hours of birth, was achieved by:

• placing subjects on a cooling blanket precooled to 5°C
• inserting an esophageal temperature probe
• adjusting the temperature of the cooling blanket to achieve an esophageal temperature of 33.5°C for 72 hours
• slow rewarming.

Abdominal-wall skin temperature was also monitored in these newborns.

Subjects in the usual care group were nursed in an incubator, with the radiant heat element adjusted to maintain skin temperature of 36.5°C to 37°C.

Investigators determined that the composite end-point of risk of death or disability at 20 months of life was significantly reduced by whole-body cooling (relative risk, 0.72; 95% confidence interval [CI], 0.54–0.95; P=.01).

Death occurred in 24% of subjects in the hypothermia group and in 37% of subjects in the usual care group (risk ratio, 0.68; 95% CI, 0.44–1.05; P=.08). The rate of cerebral palsy was 19% in the hypothermia group and 30% in the usual care group (risk ratio, 0.68; 95% CI, 0.38–1.22; P=.20).

The rate of blindness was 7% in the hypothermia group and 14% in usual care group. The rate of hearing impairment was 4% and 6% percent (P - not significant).¹

In a second clinical trial, the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial of whole-body cooling, 325 newborns with hypoxic-ischemic encephalopathy were randomized to whole-body cooling or usual care.² Whole-body cooling was achieved by nursing the infant in an incubator on a cooling blanket set at 25°C to 30°C, with the goal of maintaining a rectal temperature in the newborn of 33°C to 34°C. In this group, the heat element in the incubator was turned off.

Newborns assigned to the usual care group were nursed in an incubator with the heat element turned on and set to maintain a rectal temperature of 37°C.

The rate of death was similar in the two groups, and the rate of severe neurodevelopmental disability in each of the groups was not significantly different. Among surviving infants, however, whole-body cooling was associated with a higher rate of intact neurologic function and a diminished risk of cerebral palsy (compared to what was seen in the usual-care group). Among surviving newborns, cerebral palsy occurred in 28% of those treated with whole-body cooling and in 41% of those receiving usual care (relative risk 0.67; 95% CI, 0.47–0.96; P=.03).

No major adverse effects were observed with whole-body cooling, when compare d against usual care. A 2007 meta-analysis of four trials of therapeutic hypothermia in newborns reported a significant reduction in the composite endpoint of death or in moderate or severe neurodevelopmental disability (relative risk 0.76; 95% CI, 0.65–0.88). The number that needed to be treated to prevent one endpoint event was 6 (95% CI, 4–14).³

Note that some pediatricians remain cautious about using therapeutic hypothermia, because long-term data on the safety and efficacy of the practice have not been reported.

Impact on your practice

For decades, newborns in neonatal intensive care units received their care in warm incubators designed to maintain a body temperature of approximately 37°C. Could the standard practice of warming newborns have contributed to neurologic problems in those who suffered hypoxic-ischemic injury?

Whole-body cooling appears to reduce the rate of cerebral palsy in newborns after hypoxic-ischemic injury. For OBs, this treatment could significantly reduce their exposure to litigation that is based on a theory of hypoxic-ischemic birth injury—by reducing the number of surviving infants who have cerebral palsy.

Does your nursery have a protocol for rapidly instituting therapeutic cooling?

How does the partial pressure of arterial oxygen (PaO₂) in a newborn compare with that of an adult breathing ambient air near the summit of Mount Everest?
Take the INSTANT QUIZ.

We want to hear from you! Tell us what you think.

Major Finding: Of the 18 first-born infants, only 1 survived until discharge, while 13 survived among the 22 latter-born infants.

Data Source: A series of 17 premature multifetal deliveries in which the first fetus was born at least 24 hours before the others.

Disclosures: Dr. Murji reported no conflicts of interest.

MONTREAL — Delayed-interval delivery when the initial delivery is extremely premature carries high maternal and infant morbidity, as well as a high infant mortality, reported Dr. Ally Murji of the University of Toronto's division of maternal-fetal medicine.

“Just because we can do something, it doesn't mean it should be done,” he said in an interview.

In a study that he presented at the meeting, Dr. Murji described a series of 17 premature multifetal deliveries in which the first fetus was born at least 24 hours before the others. The mean gestational age of the first delivery was 23 weeks and 2 days.

“In our series, this procedure was reserved for the threshold of viability – extremely premature infants,” he said in an interview, explaining that the majority of the initial deliveries were precipitated by preterm premature rupture of membranes (PPROM).

Among the 17 pregnancies, 12 were twin gestations, 4 were triplets, and one was a quadruplet pregnancy, said Dr. Murji.

Forty-one percent of the pregnancies had been conceived spontaneously, with the remainder being a result of either in-vitro fertilization (47%) or ovulation induction (12%). All infants were born vaginally, except for two of the latter-born infants. In the quadruplet delivery, two babies were born within minutes of each other, followed by a latency interval and then the birth of the other two. During the interval, 88% of mothers received antibiotics and 47% received tocolysis.

Of the 18 first-born infants, only 1 survived until discharge; 13 survived among the 22 latter-born infants – a survival rate of 59%. Mean birth weight was 468 g for first-born infants and 674 g for latter-born infants.

“Clearly there is a survival benefit in having an asynchronous delivery,” noted Dr. Murji. “But these babies are not out of the woods. When you look at the absolute weights these are very small babies – babies who are very fragile. The prognosis for these babies is already guarded.”

Indeed, the infants' average stay in the neonatal intensive care unit was 104 days. Twelve of the 13 infants had at least one morbidity, including retinopathy of prematurity, intraventricular hemorrhage, patent ductus arteriosus, or sepsis, and many of them had multiple comorbidities.

Maternal morbidity also was significant. The average age of the mothers was 31 years, and complications occurred in 71% of them, with intraamniotic infection being the most common (59%). Almost half of the mothers (47%) experienced two or more complications, with abruptio placentae, postpartum hemorrhage, and blood transfusions each occurring in 18% and septic pelvic thrombophlebitis and pulmonary edema each occurring in 6%.

The findings underscore the decisions that parents and physicians must face in contemplating delayed interval delivery in the context of premature delivery of the first baby.

“Outcomes in extremely premature deliveries are meager, at best. Although we can do asynchronous delivery, is it really reasonable? Yes, there is a clear survival benefit for the latter-born infant, but this survival benefit comes at the risk of maternal morbidity and the interval in our experience has only been 1 week. And these latter-born infants have significant morbidity because they're born so prematurely,” said Dr. Murji.

Major Finding: Of the 18 first-born infants, only 1 survived until discharge, while 13 survived among the 22 latter-born infants.

Data Source: A series of 17 premature multifetal deliveries in which the first fetus was born at least 24 hours before the others.

Disclosures: Dr. Murji reported no conflicts of interest.

MONTREAL — Delayed-interval delivery when the initial delivery is extremely premature carries high maternal and infant morbidity, as well as a high infant mortality, reported Dr. Ally Murji of the University of Toronto's division of maternal-fetal medicine.

“Just because we can do something, it doesn't mean it should be done,” he said in an interview.

In a study that he presented at the meeting, Dr. Murji described a series of 17 premature multifetal deliveries in which the first fetus was born at least 24 hours before the others. The mean gestational age of the first delivery was 23 weeks and 2 days.

“In our series, this procedure was reserved for the threshold of viability – extremely premature infants,” he said in an interview, explaining that the majority of the initial deliveries were precipitated by preterm premature rupture of membranes (PPROM).

Among the 17 pregnancies, 12 were twin gestations, 4 were triplets, and one was a quadruplet pregnancy, said Dr. Murji.

Forty-one percent of the pregnancies had been conceived spontaneously, with the remainder being a result of either in-vitro fertilization (47%) or ovulation induction (12%). All infants were born vaginally, except for two of the latter-born infants. In the quadruplet delivery, two babies were born within minutes of each other, followed by a latency interval and then the birth of the other two. During the interval, 88% of mothers received antibiotics and 47% received tocolysis.

Of the 18 first-born infants, only 1 survived until discharge; 13 survived among the 22 latter-born infants – a survival rate of 59%. Mean birth weight was 468 g for first-born infants and 674 g for latter-born infants.

“Clearly there is a survival benefit in having an asynchronous delivery,” noted Dr. Murji. “But these babies are not out of the woods. When you look at the absolute weights these are very small babies – babies who are very fragile. The prognosis for these babies is already guarded.”

Indeed, the infants' average stay in the neonatal intensive care unit was 104 days. Twelve of the 13 infants had at least one morbidity, including retinopathy of prematurity, intraventricular hemorrhage, patent ductus arteriosus, or sepsis, and many of them had multiple comorbidities.

Maternal morbidity also was significant. The average age of the mothers was 31 years, and complications occurred in 71% of them, with intraamniotic infection being the most common (59%). Almost half of the mothers (47%) experienced two or more complications, with abruptio placentae, postpartum hemorrhage, and blood transfusions each occurring in 18% and septic pelvic thrombophlebitis and pulmonary edema each occurring in 6%.

The findings underscore the decisions that parents and physicians must face in contemplating delayed interval delivery in the context of premature delivery of the first baby.

“Outcomes in extremely premature deliveries are meager, at best. Although we can do asynchronous delivery, is it really reasonable? Yes, there is a clear survival benefit for the latter-born infant, but this survival benefit comes at the risk of maternal morbidity and the interval in our experience has only been 1 week. And these latter-born infants have significant morbidity because they're born so prematurely,” said Dr. Murji.

Major Finding: Of the 18 first-born infants, only 1 survived until discharge, while 13 survived among the 22 latter-born infants.

Data Source: A series of 17 premature multifetal deliveries in which the first fetus was born at least 24 hours before the others.

Disclosures: Dr. Murji reported no conflicts of interest.

MONTREAL — Delayed-interval delivery when the initial delivery is extremely premature carries high maternal and infant morbidity, as well as a high infant mortality, reported Dr. Ally Murji of the University of Toronto's division of maternal-fetal medicine.

“Just because we can do something, it doesn't mean it should be done,” he said in an interview.

In a study that he presented at the meeting, Dr. Murji described a series of 17 premature multifetal deliveries in which the first fetus was born at least 24 hours before the others. The mean gestational age of the first delivery was 23 weeks and 2 days.

“In our series, this procedure was reserved for the threshold of viability – extremely premature infants,” he said in an interview, explaining that the majority of the initial deliveries were precipitated by preterm premature rupture of membranes (PPROM).

Among the 17 pregnancies, 12 were twin gestations, 4 were triplets, and one was a quadruplet pregnancy, said Dr. Murji.

Forty-one percent of the pregnancies had been conceived spontaneously, with the remainder being a result of either in-vitro fertilization (47%) or ovulation induction (12%). All infants were born vaginally, except for two of the latter-born infants. In the quadruplet delivery, two babies were born within minutes of each other, followed by a latency interval and then the birth of the other two. During the interval, 88% of mothers received antibiotics and 47% received tocolysis.

Of the 18 first-born infants, only 1 survived until discharge; 13 survived among the 22 latter-born infants – a survival rate of 59%. Mean birth weight was 468 g for first-born infants and 674 g for latter-born infants.

“Clearly there is a survival benefit in having an asynchronous delivery,” noted Dr. Murji. “But these babies are not out of the woods. When you look at the absolute weights these are very small babies – babies who are very fragile. The prognosis for these babies is already guarded.”

Indeed, the infants' average stay in the neonatal intensive care unit was 104 days. Twelve of the 13 infants had at least one morbidity, including retinopathy of prematurity, intraventricular hemorrhage, patent ductus arteriosus, or sepsis, and many of them had multiple comorbidities.

Maternal morbidity also was significant. The average age of the mothers was 31 years, and complications occurred in 71% of them, with intraamniotic infection being the most common (59%). Almost half of the mothers (47%) experienced two or more complications, with abruptio placentae, postpartum hemorrhage, and blood transfusions each occurring in 18% and septic pelvic thrombophlebitis and pulmonary edema each occurring in 6%.

The findings underscore the decisions that parents and physicians must face in contemplating delayed interval delivery in the context of premature delivery of the first baby.

“Outcomes in extremely premature deliveries are meager, at best. Although we can do asynchronous delivery, is it really reasonable? Yes, there is a clear survival benefit for the latter-born infant, but this survival benefit comes at the risk of maternal morbidity and the interval in our experience has only been 1 week. And these latter-born infants have significant morbidity because they're born so prematurely,” said Dr. Murji.

Major Finding: Complete headache remission was achieved in 10% of those receiving 15 mL of blood, compared with 32% with 20 mL, and 26% with 30 mL.

Data Source: A 5-year, randomized, double-blind, controlled, multicenter trial involving 121 women with postepidural dural puncture headache.

Disclosures: This study was funded by grants from the Australian Society of Anaesthetists and Abbott Australasia.

SAN ANTONIO — A 20-mL or 30-mL volume of autologous blood was superior to 15 mL in a randomized controlled trial of 121 obstetric patients who requested a therapeutic epidural blood patch for headache after inadvertent dural puncture during epidural insertion.

“We concluded … that an attempt to inject at least 20 mL should be made,” said Dr. Michael Paech, the Winthrop Professor and Chair of Obstetric Anesthesia at the University of Western Australia, Perth.

Although 20 mL is the most commonly used volume for therapeutic epidural blood patch (EBP), some experts have advocated using smaller or larger volumes. A 2002 Cochrane review concluded that “adequately powered, randomized trials (including at least a few hundred patients) are required before reliable conclusions can be drawn about the role of epidural blood patching in the prevention and treatment of post-dural puncture headache” (Cochrane Database Syst Rev. 2002;(2):CD001791). In a recent update, the Cochrane group still did not recommend prophylactic EBP but concluded that “therapeutic epidural blood patch showed a benefit over conservative treatment, based on the limited available evidence” (Cochrane Database Syst Rev. 2010;(1):CD001791).htttil now, the largest study of therapeutic EBP involved 33 patients, Dr. Paech noted.

The current study took place at 10 international centers between September 2004 and August 2009. The 121 women were randomized to 15 mL, 20 mL or 30 mL of blood, and were stratified by center and by receipt of the EBP at less than or longer than 48 hours after dural puncture. They were placed in the lateral position, injected at a rate of 5 mL per 15 seconds, and remained supine for 2 hours after.

There were no significant differences among the three dosage groups in the composite end point of complete response (resolved within 4 hours with no recurrence) or partial response (severity reduced or recurrence), which was achieved by 61% of the 15-mL group, 73% of the 20-mL group and 67% of the 30-mL group.

However, complete remission with no recurrence was far less common in the 15-mL group, with just 10% achieving that end point, compared with 32% of the 20-mL group and 26% of the 30-mL group. Compared with the 15-mL group, the odds ratios for complete headache relief were 4.7 for 20 mL and 3.6 for 30 mL, Dr. Paech reported.

There were no significant differences among the groups in functional assessment of headache impact, time to return of headache (overall mean 98 hours), time from EBP to hospital discharge, or incidence of repeat EBP. About half of the patients experienced back pain during the EBP injection, while back pain after the EBP occurred in about 85% overall, did not differ significantly among the groups, and was usually of low intensity, he said.

The proportions still suffering from moderate to severe back pain after 5 days did not differ significantly, although it was greater in the 15-mL group at 23%, compared with 12% of the 20-mL group and 11% of the 30-mL group..

During the question-and-answer period, Dr. Paech noted that the odds of partial or complete relief of headache if EBP was performed more than 48 hours (about two-thirds of all the subjects) from the dural puncture was 3.2 times greater than if done within 48 hours, a significant difference.

Major Finding: Complete headache remission was achieved in 10% of those receiving 15 mL of blood, compared with 32% with 20 mL, and 26% with 30 mL.

Data Source: A 5-year, randomized, double-blind, controlled, multicenter trial involving 121 women with postepidural dural puncture headache.

Disclosures: This study was funded by grants from the Australian Society of Anaesthetists and Abbott Australasia.

SAN ANTONIO — A 20-mL or 30-mL volume of autologous blood was superior to 15 mL in a randomized controlled trial of 121 obstetric patients who requested a therapeutic epidural blood patch for headache after inadvertent dural puncture during epidural insertion.

“We concluded … that an attempt to inject at least 20 mL should be made,” said Dr. Michael Paech, the Winthrop Professor and Chair of Obstetric Anesthesia at the University of Western Australia, Perth.

Although 20 mL is the most commonly used volume for therapeutic epidural blood patch (EBP), some experts have advocated using smaller or larger volumes. A 2002 Cochrane review concluded that “adequately powered, randomized trials (including at least a few hundred patients) are required before reliable conclusions can be drawn about the role of epidural blood patching in the prevention and treatment of post-dural puncture headache” (Cochrane Database Syst Rev. 2002;(2):CD001791). In a recent update, the Cochrane group still did not recommend prophylactic EBP but concluded that “therapeutic epidural blood patch showed a benefit over conservative treatment, based on the limited available evidence” (Cochrane Database Syst Rev. 2010;(1):CD001791).htttil now, the largest study of therapeutic EBP involved 33 patients, Dr. Paech noted.

The current study took place at 10 international centers between September 2004 and August 2009. The 121 women were randomized to 15 mL, 20 mL or 30 mL of blood, and were stratified by center and by receipt of the EBP at less than or longer than 48 hours after dural puncture. They were placed in the lateral position, injected at a rate of 5 mL per 15 seconds, and remained supine for 2 hours after.

There were no significant differences among the three dosage groups in the composite end point of complete response (resolved within 4 hours with no recurrence) or partial response (severity reduced or recurrence), which was achieved by 61% of the 15-mL group, 73% of the 20-mL group and 67% of the 30-mL group.

However, complete remission with no recurrence was far less common in the 15-mL group, with just 10% achieving that end point, compared with 32% of the 20-mL group and 26% of the 30-mL group. Compared with the 15-mL group, the odds ratios for complete headache relief were 4.7 for 20 mL and 3.6 for 30 mL, Dr. Paech reported.

There were no significant differences among the groups in functional assessment of headache impact, time to return of headache (overall mean 98 hours), time from EBP to hospital discharge, or incidence of repeat EBP. About half of the patients experienced back pain during the EBP injection, while back pain after the EBP occurred in about 85% overall, did not differ significantly among the groups, and was usually of low intensity, he said.

The proportions still suffering from moderate to severe back pain after 5 days did not differ significantly, although it was greater in the 15-mL group at 23%, compared with 12% of the 20-mL group and 11% of the 30-mL group..

During the question-and-answer period, Dr. Paech noted that the odds of partial or complete relief of headache if EBP was performed more than 48 hours (about two-thirds of all the subjects) from the dural puncture was 3.2 times greater than if done within 48 hours, a significant difference.

Major Finding: Complete headache remission was achieved in 10% of those receiving 15 mL of blood, compared with 32% with 20 mL, and 26% with 30 mL.

Data Source: A 5-year, randomized, double-blind, controlled, multicenter trial involving 121 women with postepidural dural puncture headache.

Disclosures: This study was funded by grants from the Australian Society of Anaesthetists and Abbott Australasia.

SAN ANTONIO — A 20-mL or 30-mL volume of autologous blood was superior to 15 mL in a randomized controlled trial of 121 obstetric patients who requested a therapeutic epidural blood patch for headache after inadvertent dural puncture during epidural insertion.

“We concluded … that an attempt to inject at least 20 mL should be made,” said Dr. Michael Paech, the Winthrop Professor and Chair of Obstetric Anesthesia at the University of Western Australia, Perth.

Although 20 mL is the most commonly used volume for therapeutic epidural blood patch (EBP), some experts have advocated using smaller or larger volumes. A 2002 Cochrane review concluded that “adequately powered, randomized trials (including at least a few hundred patients) are required before reliable conclusions can be drawn about the role of epidural blood patching in the prevention and treatment of post-dural puncture headache” (Cochrane Database Syst Rev. 2002;(2):CD001791). In a recent update, the Cochrane group still did not recommend prophylactic EBP but concluded that “therapeutic epidural blood patch showed a benefit over conservative treatment, based on the limited available evidence” (Cochrane Database Syst Rev. 2010;(1):CD001791).htttil now, the largest study of therapeutic EBP involved 33 patients, Dr. Paech noted.

The current study took place at 10 international centers between September 2004 and August 2009. The 121 women were randomized to 15 mL, 20 mL or 30 mL of blood, and were stratified by center and by receipt of the EBP at less than or longer than 48 hours after dural puncture. They were placed in the lateral position, injected at a rate of 5 mL per 15 seconds, and remained supine for 2 hours after.

There were no significant differences among the three dosage groups in the composite end point of complete response (resolved within 4 hours with no recurrence) or partial response (severity reduced or recurrence), which was achieved by 61% of the 15-mL group, 73% of the 20-mL group and 67% of the 30-mL group.

However, complete remission with no recurrence was far less common in the 15-mL group, with just 10% achieving that end point, compared with 32% of the 20-mL group and 26% of the 30-mL group. Compared with the 15-mL group, the odds ratios for complete headache relief were 4.7 for 20 mL and 3.6 for 30 mL, Dr. Paech reported.

There were no significant differences among the groups in functional assessment of headache impact, time to return of headache (overall mean 98 hours), time from EBP to hospital discharge, or incidence of repeat EBP. About half of the patients experienced back pain during the EBP injection, while back pain after the EBP occurred in about 85% overall, did not differ significantly among the groups, and was usually of low intensity, he said.

The proportions still suffering from moderate to severe back pain after 5 days did not differ significantly, although it was greater in the 15-mL group at 23%, compared with 12% of the 20-mL group and 11% of the 30-mL group..

During the question-and-answer period, Dr. Paech noted that the odds of partial or complete relief of headache if EBP was performed more than 48 hours (about two-thirds of all the subjects) from the dural puncture was 3.2 times greater than if done within 48 hours, a significant difference.

SAN ANTONIO — Pregnancy-related subarachnoid hemorrhage presented most often in the postpartum period and often with severe headache, analyses of both nationwide and single-institution datasets revealed.

In an analysis of data from the Nationwide Inpatient Sample – an administrative dataset containing information on 20% of United States hospital admissions – SAH occurred at a rate of 5.6 per 100,000 deliveries and 5.0 per 100,000 pregnancy-related admissions. Two-thirds of these occurred in the postpartum period, Dr. Vanessa A. Olbrecht said.

Although rare, the incidence of SAH is increased twofold among women in the intrapartum/peripartum periods compared with the general population, and it is the second leading cause of indirect maternal death after cardiac disease. SAH needs to be considered in the differential diagnosis of postpartum headache, according to Dr. Olbrecht.

She and her associates at Massachusetts General Hospital used two data sources to investigate the epidemiology of SAH in pregnancy. From the NIS, they extracted all pregnancy-related admissions for women aged 15–44 years during 1997–2006, and identified all of those admissions with a primary or secondary diagnosis of SAH.

The second analysis was a comprehensive retrospective review of their own institution's experience with pregnancy-related SAH from 1992 through 2009. Here, they included only patients with SAH as the primary pathology, Dr. Olbrecht explained.

In the NIS, there were an estimated 2,254 cases of pregnancy-related SAH in the United States during the study period.

There was a geometric increase in SAH with age, with a doubling of the incidence from those aged 35–39 years to 40–44 years and odds ratios of 1.7 to 2.3 per every 10-year increase in age.

In a logistic regression analysis, eclampsia was the single biggest predictor of pregnancy-related SAH, with an “impressive” odds ratio of 88.4. Other significant and independent predictors included coagulopathy (odds ratio 7.2), preeclampsia superimposed on preexisting hypertension (4.2), severe preeclampsia (3.1), tobacco use (2.6), pre-existing hypertension (2.4), African-American race (2.4, compared with Caucasians), mild preeclampsia (2.1), and Hispanic race (1.6).

Compared with an age-matched cohort of non-pregnant women with SAH, the pregnant women with SAH had significantly lower in-hospital mortality, with a rate of 10.7% versus 18.7%. The proportion discharged somewhere other than home was 35.2% among the pregnant women with SAH vs. 48% among those with non-pregnancy related SAH. And the percentage who had aneurysm clipping/coiling – used as a proxy for aneurysmal SAH – was 12.1% in the pregnancy-related SAH group, compared with 44.2% among the non-pregnant SAH patients.

At Massachusetts General, there were 11 cases of SAH during the 17-year study period. Nine of the 11 had cesarean sections, and only 2 had vaginal deliveries. The women ranged in age from 19 to 42, with one-third over the age of 35 at the time of diagnosis. Half were Caucasian, 3 were African-American, and 2 were Hispanic. As in the NIS, two-thirds of the SAH occurred in the postpartum period, at a median of postpartum day 8.

The majority (9) presented with a sudden severe headache, and one-fourth (3) had seizures. Three cases were aneurysmal and were treated with craniotomy, and 2 were associated with venous sinus thrombosis. One patient died, and two were discharged home with significant neurologic deficits.

None of the study authors reported having relevant conflicts of interest.

SAH needs to be considered in the differential diagnosis of postpartum headache.

Source DR. OLBRECHT

SAN ANTONIO — Pregnancy-related subarachnoid hemorrhage presented most often in the postpartum period and often with severe headache, analyses of both nationwide and single-institution datasets revealed.

In an analysis of data from the Nationwide Inpatient Sample – an administrative dataset containing information on 20% of United States hospital admissions – SAH occurred at a rate of 5.6 per 100,000 deliveries and 5.0 per 100,000 pregnancy-related admissions. Two-thirds of these occurred in the postpartum period, Dr. Vanessa A. Olbrecht said.

Although rare, the incidence of SAH is increased twofold among women in the intrapartum/peripartum periods compared with the general population, and it is the second leading cause of indirect maternal death after cardiac disease. SAH needs to be considered in the differential diagnosis of postpartum headache, according to Dr. Olbrecht.

She and her associates at Massachusetts General Hospital used two data sources to investigate the epidemiology of SAH in pregnancy. From the NIS, they extracted all pregnancy-related admissions for women aged 15–44 years during 1997–2006, and identified all of those admissions with a primary or secondary diagnosis of SAH.

The second analysis was a comprehensive retrospective review of their own institution's experience with pregnancy-related SAH from 1992 through 2009. Here, they included only patients with SAH as the primary pathology, Dr. Olbrecht explained.

In the NIS, there were an estimated 2,254 cases of pregnancy-related SAH in the United States during the study period.

There was a geometric increase in SAH with age, with a doubling of the incidence from those aged 35–39 years to 40–44 years and odds ratios of 1.7 to 2.3 per every 10-year increase in age.

In a logistic regression analysis, eclampsia was the single biggest predictor of pregnancy-related SAH, with an “impressive” odds ratio of 88.4. Other significant and independent predictors included coagulopathy (odds ratio 7.2), preeclampsia superimposed on preexisting hypertension (4.2), severe preeclampsia (3.1), tobacco use (2.6), pre-existing hypertension (2.4), African-American race (2.4, compared with Caucasians), mild preeclampsia (2.1), and Hispanic race (1.6).

Compared with an age-matched cohort of non-pregnant women with SAH, the pregnant women with SAH had significantly lower in-hospital mortality, with a rate of 10.7% versus 18.7%. The proportion discharged somewhere other than home was 35.2% among the pregnant women with SAH vs. 48% among those with non-pregnancy related SAH. And the percentage who had aneurysm clipping/coiling – used as a proxy for aneurysmal SAH – was 12.1% in the pregnancy-related SAH group, compared with 44.2% among the non-pregnant SAH patients.

At Massachusetts General, there were 11 cases of SAH during the 17-year study period. Nine of the 11 had cesarean sections, and only 2 had vaginal deliveries. The women ranged in age from 19 to 42, with one-third over the age of 35 at the time of diagnosis. Half were Caucasian, 3 were African-American, and 2 were Hispanic. As in the NIS, two-thirds of the SAH occurred in the postpartum period, at a median of postpartum day 8.

The majority (9) presented with a sudden severe headache, and one-fourth (3) had seizures. Three cases were aneurysmal and were treated with craniotomy, and 2 were associated with venous sinus thrombosis. One patient died, and two were discharged home with significant neurologic deficits.

None of the study authors reported having relevant conflicts of interest.

SAH needs to be considered in the differential diagnosis of postpartum headache.

Source DR. OLBRECHT

SAN ANTONIO — Pregnancy-related subarachnoid hemorrhage presented most often in the postpartum period and often with severe headache, analyses of both nationwide and single-institution datasets revealed.

In an analysis of data from the Nationwide Inpatient Sample – an administrative dataset containing information on 20% of United States hospital admissions – SAH occurred at a rate of 5.6 per 100,000 deliveries and 5.0 per 100,000 pregnancy-related admissions. Two-thirds of these occurred in the postpartum period, Dr. Vanessa A. Olbrecht said.

Although rare, the incidence of SAH is increased twofold among women in the intrapartum/peripartum periods compared with the general population, and it is the second leading cause of indirect maternal death after cardiac disease. SAH needs to be considered in the differential diagnosis of postpartum headache, according to Dr. Olbrecht.

She and her associates at Massachusetts General Hospital used two data sources to investigate the epidemiology of SAH in pregnancy. From the NIS, they extracted all pregnancy-related admissions for women aged 15–44 years during 1997–2006, and identified all of those admissions with a primary or secondary diagnosis of SAH.

The second analysis was a comprehensive retrospective review of their own institution's experience with pregnancy-related SAH from 1992 through 2009. Here, they included only patients with SAH as the primary pathology, Dr. Olbrecht explained.

In the NIS, there were an estimated 2,254 cases of pregnancy-related SAH in the United States during the study period.

There was a geometric increase in SAH with age, with a doubling of the incidence from those aged 35–39 years to 40–44 years and odds ratios of 1.7 to 2.3 per every 10-year increase in age.

In a logistic regression analysis, eclampsia was the single biggest predictor of pregnancy-related SAH, with an “impressive” odds ratio of 88.4. Other significant and independent predictors included coagulopathy (odds ratio 7.2), preeclampsia superimposed on preexisting hypertension (4.2), severe preeclampsia (3.1), tobacco use (2.6), pre-existing hypertension (2.4), African-American race (2.4, compared with Caucasians), mild preeclampsia (2.1), and Hispanic race (1.6).

Compared with an age-matched cohort of non-pregnant women with SAH, the pregnant women with SAH had significantly lower in-hospital mortality, with a rate of 10.7% versus 18.7%. The proportion discharged somewhere other than home was 35.2% among the pregnant women with SAH vs. 48% among those with non-pregnancy related SAH. And the percentage who had aneurysm clipping/coiling – used as a proxy for aneurysmal SAH – was 12.1% in the pregnancy-related SAH group, compared with 44.2% among the non-pregnant SAH patients.

At Massachusetts General, there were 11 cases of SAH during the 17-year study period. Nine of the 11 had cesarean sections, and only 2 had vaginal deliveries. The women ranged in age from 19 to 42, with one-third over the age of 35 at the time of diagnosis. Half were Caucasian, 3 were African-American, and 2 were Hispanic. As in the NIS, two-thirds of the SAH occurred in the postpartum period, at a median of postpartum day 8.

The majority (9) presented with a sudden severe headache, and one-fourth (3) had seizures. Three cases were aneurysmal and were treated with craniotomy, and 2 were associated with venous sinus thrombosis. One patient died, and two were discharged home with significant neurologic deficits.

None of the study authors reported having relevant conflicts of interest.

SAH needs to be considered in the differential diagnosis of postpartum headache.

Source DR. OLBRECHT